Abstract

In lupus erythematosus, elevated serum creatinine levels and urinary abnormalities
implicate a kidney disorder, which may not always be lupus nephritis as defined by
the current classification of the International Society of Nephrology/Renal Pathology
Society. The signs of renal dysfunction may be caused by lupusunrelated renal injury
such as drug toxicity or infection or by lupus-associated mechanisms that are not
part of the classification, such as minimal change nephrotic syndrome or thrombotic
microangiopathy. The latter seems to complicate lupus nephritis more frequently than
previously thought. An unbiased assessment of kidney disease in lupus requires a kidney
(re-)biopsy to define the appropriate management.

Editorial

In the previous issue of Arthritis Research & Therapy, Song and colleagues [1] discussed specific kidney abnormalities in patients with lupus erythematosus (LE).
LE can manifest as cutaneous LE or as a systemic disorder (systemic lupus erythematosus,
or SLE) [2]. In patients with LE, renal abnormalities, such as elevated serum creatinine levels
or urinary abnormalities, require further diagnostic work-up because they may indicate
renal involvement in SLE or an unrelated form of renal disease [3]. Furthermore, renal symptoms may indicate flares of disease activity in patients
with established lupus nephritis but may also reflect renal injury due to concomitant
toxicity or infectious disease. How should lupus nephritis be defined? The current
classification of the International Society of Nephrology/Renal Pathology Society
(ISN/RPS) is based on the phenotype of immune complex glomerulonephritis that depends
on the predominant site of immune complex deposition within the glomerulus and on
different stages of acute (and potentially reversible) injury and chronic (and potentially
irreversible) scarring [4]. The article on ISN/RPS classification of lupus nephritis [4] emphasizes the importance of including all other forms of kidney injury, separate
from immune complex-mediated glomerulonephritis, in the diagnostic evaluation of the
renal biopsy in SLE, including thrombotic microangiopathy (TMA). The article advocates
that 'the extent, severity, and type of tubulointerstitial injury (tubular atrophy,
interstitial fibrosis, and chronic lesions) and vascular disease (vascular deposits,
thrombi, vasculitis, sclerosis) should also be documented and graded (mild, moderate,
severe) in the diagnostic line' [4].

Song and colleagues [1] presented a detailed histopathological analysis of a series of 148 patients with
biopsy-proven lupus nephritis, focusing on the prevalence of TMA. The authors defined
TMA by light microscopy as interlobular artery, arteriole, and glomerular capillary
lesions, including endothelial swelling, lumen narrowing or obliteration, and thrombi
formation. Electron microscopic TMA criteria are swelling of glomerular endothelial
cells, detachment from glomerular basement membrane, and widening of the subendothelial
space. Fibrin staining identifies acute microthrombi, whereas mucoid changes and onionskin
lesions of arterioles were considered chronic. The authors found such TMA lesions
in 36 out of the 148 patients with lupus nephritis [1]. In some of these cases, TMA was a manifestation of associated systemic autoimmune
states such as the anti-phospholipid antibody syndrome, scleroderma, or thrombotic
thrombocytopenic purpura, which have specific diagnostic criteria and are not included
as a specific category in the current ISN/RPS classification of lupus nephritis [4].

In the majority of cases, TMA was associated with immune complex-mediated forms of
lupus nephritis. According to the authors, such cases can be missed easily unless
fibrin immunostaining is performed. TMA results from severe injury to the vascular
endothelium, which Song and colleagues [1] found to be associated with poorer renal outcomes as compared with patients with
non-TMA lupus nephritis. As such, reporting TMA in the renal biopsy and defining the
ISN/RPS class are important, even though the management implications remain unclear
unless a causative disorder such as the anti-phospholipid antibody syndrome (anticoagulation),
overlap syndrome with scleroderma (angiotensin inhibition), or thrombotic thrombocytopenic
purpura (plasma exchange) can be identified.

The report by Song and colleagues reminds us that, in LE, elevated serum creatinine
levels or urinary abnormalities (or both) may not always represent immune complex
glomerulonephritis (that is, 'lupus nephritis'). In addition, patients with SLE can
develop other kidney disorders that may be related or unrelated to SLE and SLE management
(Table 1) [3].